Experts: Wheat Sensitivity Is Real

Medically Reviewed by Brunilda Nazario, MD on November 23, 2016
From the WebMD Archives

Nov. 23, 2016 -- When Kathy Pothier began eating gluten-free in 2012, some friends thought it was an inconvenience. So Pothier -- determined to see if the diet could relieve her painful arthritis symptoms, stiff neck, and headaches -- took her own food when she visited for dinner.

Because the 47-year-old landscaper from Amesbury, MA, doesn't have celiac disease or wheat allergy, her friends dismissed her diet as the latest fad. But Pothier says that going gluten-free gave her relief from her pain. "When I stopped [gluten], it all went away within 3 months," she says.

Emerging research is suggesting that some people without a diagnosis of either celiac disease or wheat allergy may indeed be wheat-sensitive -- and the gluten may not be what’s causing their problems. They may have bloating, pain, gas, and diarrhea that are hallmark symptoms of celiac disease. Or they may also have headaches and inflammatory symptoms like Pothier’s.

“I think there is now enough data to say that there are people out there who do have symptoms that are related to either wheat or gluten who are not [diagnosed with] celiac and not classic wheat allergy," says Joseph Murray, MD, a professor of medicine and gastroenterology at Mayo Clinic, Rochester, MN.

"It's probably relatively rare," he says, pegging it at about 1% of the population, or about 3 million people in the U.S.

Celiac is diagnosed with a blood test or intestinal biopsy; wheat allergies are diagnosed with a skin or blood test. Until about 5 years ago, if people were not diagnosed with either, they were told they had no reason to be on a gluten-free diet, says Alessio Fasano, MD, director of the Center for Celiac Research and Treatment at Massachusetts General Hospital.

Since then, he says, study after study has found evidence that non-celiac gluten sensitivity may, indeed, be real.

"People have dismissed non-celiac gluten sensitivity as a fad," says William F. Balistreri, MD, a doctor at the Cincinnati Children's Hospital Medical Center. "But there may well be an immunologic basis" for it, he says.

And the protein gluten may not be the whole story, Murray and others say. Some people could be reacting to other components in the wheat.

"Wheat is a very complicated organism," Murray says. Experts now say there may be several subgroups of people with wheat sensitivity, each reacting to a different part of the wheat.

Wheat and Health: What's Under Study

Among the recent studies:

  • The immune systems of people who don't have celiac or wheat allergy but still report GI and other symptoms after eating wheat products may still be reacting to the grains, Columbia University researchers found. Researchers compared 80 people with non-celiac wheat sensitivity, 40 with celiac disease, and 40 healthy people. The immune system reaction in the gluten-sensitive people was different from that of the celiac patients, but it was still linked to damage to the cells in their intestines. When they cut wheat from their diets for 6 months, their immune system functioning went back to normal, and symptoms improved. The difference in the reaction may help explain why these people report symptoms like headaches in addition to GI symptoms.
    "The take-home message of our study's findings is that there are objective biological changes in a significant number of individuals who report sensitivity to wheat without having celiac disease," says study leader Armin Alaedini, PhD, an assistant professor of medicine at Columbia University Medical Center.
  • For some, proteins found in wheat, called ATIs (amylase-trypsin inhibitors), may be triggering the symptoms. These proteins, which make up about 4% of wheat, act as the grain's natural pesticide, warding off meal bugs and other invaders. They can also cause GI trouble. "ATIs are very important food components that can worsen chronic disease," says Detlef Schuppan, MD, PhD, a professor of medicine at Harvard Medical School and a researcher at University Medical Center of the Johannes Gutenberg University in Mainz, Germany.
    His research on animals showed that the proteins can trigger powerful immune reactions in the gut, explaining some of the symptoms of non-celiac gluten sensitivity, he says. It may also help explain other inflammation-related conditions, such as rheumatoid arthritis, MS, and asthma, Schuppan says.
  • Carbohydrates in wheat that cause intestinal gas have also been implicated. However, some researchers now believe they cause, at most, a mild wheat intolerance.


Would Diet Changes Help?

Researchers who have looked at whether gluten- or wheat-free diets can make a difference have found that they do sometimes help. Non-celiac wheat sensitivity has been found in some patients with irritable bowel syndrome, so some studies have targeted them to test a gluten-free diet.

In one, Murray and his colleagues tested the diet on people who had irritable bowel syndrome with diarrhea. "We found that a group of them got better," he says. About half of those on the gluten-free diet had genes linked to celiac disease but were not diagnosed with celiac; those were the patients who got better. He suspects they may have a mild immune reaction similar to that seen in celiac disease.

Advice for the Wheat-Sensitive

Anyone who thinks they have a problem with wheat should first get tested for celiac disease, Murray says. If they try to cut down or eliminate gluten before getting the blood test, it may produce false negative results.

If you test negative for celiac and no one can identify an alternative cause, such as wheat allergy, for your symptoms, ''it might be realistic to go on a gluten-free diet," Murray says. However, he says, ''you must be open-minded to failure. If it doesn't work after 2 weeks, or 4 for sure, it's not going to work.”

There is no test yet to determine what element in wheat that people are sensitive to. But those tests are in the works. Fasano is working on a test for people who react to the wheat protein ATIs.

Experts predict that in the future, it may be possible to pinpoint which part of the wheat is triggering a reaction, so people can learn what foods to avoid to stay symptom-free.

Show Sources


Gut: "Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease."

Gastroenterology: "Nonceliac gluten and wheat sensitivity."

Gastroenterology: "A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function."

Joseph Murray, MD, professor of medicine and gastroenterology, Mayo Clinic, Rochester, MN.                                              

William F. Balistreri, MD, physician, Cincinnati Children's Hospital Medical Center.

Detlef Schuppan, MD, PhD, professor of medicine, Harvard Medical School; researcher, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Alessio Fasano, MD, director of the Center for Celiac Research and Treatment, Massachusetts General Hospital.

Armin Alaedini, PhD, assistant professor of medicine, director of laboratory research, Celiac Disease Center, Columbia University Medical Center, New York.

Kathy Pothier, 47, landscaper in Amesbury, MA.

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